ES2829224T3 - Cartridge to distribute a liquid - Google Patents

Abstract

A cartridge (1100, 1300, 1350, 1902 ', 1902 ") for dispensing liquid (1302, 1302', 1516), comprising: - a reservoir (1122) filled with liquid; - a reservoir conduit (1124) for connecting the reservoir with a valve; - an outlet conduit (1128) to distribute the liquid; and - the valve (1100), in which the valve is a sliding valve (1110), in which the valve comprises a pumping chamber (1118) for pumping the liquid, in which the valve comprises a pumping chamber conduit (1120), in which the sliding valve is configured to translate the pumping chamber conduit (1120), in which the valve is configured to locate the pumping chamber conduit to connect with the reservoir conduit, wherein the valve is further configured to locate the pumping chamber conduit to connect with the outlet conduit, wherein the pumping chamber conduit is permanently connected to the pumping chamber, in which the slide valve comprises a piston (1114) and a housing (1117) having a volume (1116) to receive the piston, in which the piston can be operated for translation movement within the volume, in which the piston comprises the passage pumping chamber, in which the pumping chamber is a cavity within the piston, in which the piston is configured to translate the pumping chamber conduit to connect with the reservoir conduit and disconnect from the outlet conduit, in the that the piston is further configured to translate the pumping chamber conduit to connect with the outlet conduit and disconnect from the reservoir conduit; and - a plunger (1108) arranged in a portion of the piston forming the cavity, the plunger being configured to change a volume of the pumping chamber, wherein the pumping chamber is formed by the cavity and the plunger, in the that the static friction between the piston and the volume housing (1117) to receive the piston is greater than the static friction between the piston and the part of the piston that forms the cavity.

Description

DESCRIPTION

Cartridge to distribute a liquid

Field of the invention

The invention relates to cartridges for dispensing a liquid. The invention further relates to an automatic analyzer for dispensing the liquid using the cartridge.

Background and Related Art

In medical laboratories, in vitro diagnostics are commonly performed on biological samples such as blood, urine, blood plasma, and saliva. Such tests can be done manually using pipettes or can be done using an automated analyzer. Automated analyzers can automatically add reagents to the biological sample and can measure one or more parameters of the biological sample during analysis. Automatic analyzers are known in the prior art. For example, European patent EP 1959 257 A2 discloses an automatic analyzer that includes a mechanism for containing reagent cassettes for containing a plurality of reagent cassettes.

United States patent US 7,955,302 B2 discloses a dosing device for an infusion system comprising a dosing unit having a variable volume and at least one opening in liquid connection with the variable volume.

Summary

The invention provides a cartridge for dispensing liquid according to claim 1, an automatic analyzer according to claim 7 and a method for operating a cartridge according to claim 10. Embodiments are described in the dependent claims.

The present invention provides a cartridge for dispensing a liquid. In some embodiments, the cartridge comprises a rotary valve that can be moved circularly to locate a pump chamber conduit leading from a pump chamber. Rotation of the rotary valve enables the pump chamber conduit to be connected to one of a variety of other conduits. The pump chamber is formed by a cavity within the rotary valve and by a plunger that can be operated to change the volume of the pump chamber. In some other embodiments a linear valve is used to locate the pump chamber conduit.

The cartridge comprises a reservoir for storing the liquid and an outlet conduit for dispensing a liquid. A reservoir conduit connects the reservoir to the valve. In some embodiments, the outlet conduit connects an outlet nozzle to the valve. As the valve moves to different positions, the pumping chamber conduit can be located in the reservoir conduit or the outlet conduit. In some embodiments, the valve and plunger can be operated or actuated independently of one another. The embodiments of this cartridge may have the advantage that they can be operated so that the cartridge does not leak any liquid or that the loss of liquid due to priming can be reduced.

A controller as used herein encompasses a device, machine, or apparatus for controlling the operation and / or function of one or more other devices. Examples of a controller may include, but are not limited to: a computer, a processor, an embedded system or controller, a programmable logic controller, and a microcontroller. A "computing device" or "computer" as used herein encompasses any device that comprises a processor. A 'processor' as used herein encompasses an electronic component that can execute a machine-executable instruction or program.

A 'computer-readable storage medium' as used herein encompasses any tangible storage medium that can store instructions that are executable by a processor of a computing device. The computer-readable storage medium may be referred to as a non-transient computer-readable storage medium.

'Computer memory' or 'memory' is an example of a computer-readable storage medium. Computer memory is any memory that is directly accessible to a processor or other controller. 'Computer storage' or 'storage' is an example of a computer-readable storage medium. Computer storage is any non-volatile computer-readable storage medium.

A "user interface" as used herein is an interface that allows a user or operator to interact with a computer or computer system.

A 'computer equipment interface' as used herein encompasses an interface that enables a processor or other controller to interact with and / or control a computing device and / or external apparatus. An interface Computer equipment can allow a processor to send control signals or instructions to a computing device and / or external apparatus. The computer equipment interface may enable the processor or other controller to receive sensor data and control the distribution of the liquid. The computer interface can be used to form a closed control loop in some embodiments.

In one aspect, the invention provides a cartridge for dispensing liquid. The cartridge comprises a valve. The valve comprises a pumping chamber for pumping the liquid. The valve can be operated to locate a pump chamber conduit. The pump chamber conduit connects to the pump chamber. The valve further comprises a plunger operable to change the volume of the pumping chamber. The valve further comprises a reservoir conduit (124, 1214) for connecting the reservoir to the valve, wherein the valve can be operated to position the pump chamber conduit to connect with the reservoir conduit. The valve further comprises an outlet conduit for distributing the liquid. The rotary valve can be further operated to rotate the pumping chamber conduit to connect with the outlet conduit.

In another aspect, a cartridge is provided for dispensing liquid. The cartridge comprises a rotary valve. The rotary valve comprises a pumping chamber for pumping the liquid. The rotary valve can be operated to rotate a pumping chamber conduit. The pump chamber conduit connects to the pump chamber. In other words, there is a rotary valve that has a pump chamber conduit connected to a pump chamber within it. By rotating the rotary valve, the pump chamber conduit can be rotated in different positions, thus allowing the pump chamber to be connected to other conduits.

The cartridge further comprises a plunger operable to change the volume of the pump chamber. The rotary valve and plunger can be operated to actuate independently. In other words, the plunger and the rotary valve can be operated so that the plunger can be used to change the volume of the pumping chamber without affecting the position of the rotary valve and vice versa. This can enable a greater set of pumping actions through the pumping chamber.

The cartridge further comprises a reservoir for storing the liquid. The tank can be built in a variety of ways. In some embodiments, the reservoir may be a hard-walled chamber, preferably made of plastics using injection molding or thermoforming processes. In some embodiments, the reservoir can be a chamber with a flexible wall. In some embodiments, the reservoir could be a bag or sack. In other embodiments, the reservoir could be a bag or sack supported by an outer container. In other embodiments, the reservoir could be a tube.

The cartridge further comprises a reservoir conduit for connecting the reservoir to the rotary valve. The rotary valve can be operated to rotate the pumping chamber conduit to connect with the reservoir conduit. When the pumping chamber conduit is rotated into the correct position, then there is communication between the pumping chamber and the reservoir.

The cartridge further comprises an outlet conduit to distribute the liquid and to connect to the rotary valve. The rotary valve can be further operated to rotate the pumping chamber conduit to connect to the outlet conduit. This embodiment can have the advantage that a wide variety of pumping actions can be performed with the pumping chamber by controlling the rotary position of the rotary valve and properly operating the plunger. For example, the rotary valve can be positioned so that the pump chamber conduit connects to the reservoir conduit. In this case, the plunger can be used to draw liquid from the reservoir to the pumping chamber or it can be used to pump the liquid from the pumping chamber back to the reservoir.

The present embodiment can enable other types of actions using the pumping chamber. For example, when the pump chamber conduit is aligned or connected with the reservoir conduit, the plunger can be used repeatedly to increase and decrease the volume of the pump chamber. This can allow the liquid to mix within the reservoir. Additionally, the ability to return liquid to the reservoir can reduce the amount of liquid that is wasted.

This embodiment can also enable a so-called low-waste priming or no-waste priming function of the pumping chamber, whereby nothing or possibly only a very small amount of the liquid is wasted or discarded when liquid is pumped out through. outlet duct. For example, when the pump chamber conduit connects to the outlet conduit, the plunger can be used to decrease the volume of the pump chamber and thereby force or distribute liquid out through the outlet conduit. During the procedure of doing this, there may be liquid within the outlet conduit that does not exit the outlet conduit. After the correct amount of liquid has been dispensed, the plunger can then be used to increase the volume of the pump chamber, thereby removing liquid that may remain within the outlet conduit back into the pump chamber. pumping. Liquid could then be contained within the pumping chamber or, if the rotary valve is rotated in alignment with the reservoir conduit, the liquid that was previously within the outlet conduit can be pumped back into the reservoir.

The rotary valve can also provide a means to prevent liquid from accidentally escaping from the reservoir. For example, the rotary valve can be rotated in some embodiments to a position where it does not align with the outlet conduit or the reservoir conduit. This can prevent liquid and / or gas from exiting the outlet conduit and / or liquid and / or gas in a reservoir from escaping or draining into the pumping chamber.

In another embodiment, the cartridge further comprises an outlet nozzle connected to the outlet conduit. An outlet nozzle as used herein includes a nozzle design to minimize liquid waste and can enable drops to fall cleanly during the dosing procedure. For example, in a simple tube, a drop of the liquid can be suspended on the outside of the nozzle after the plunger is used to decrease the volume of the pump chamber. The shape or function of the outlet nozzle can be designed to reduce the chances that a drop of the liquid will become suspended from it. For example, the outlet nozzle may have a so-called duckbill conformation and be a duckbill nozzle.

In other embodiments, the cartridge may have additional reservoirs and additional reservoir lines that enable the pump chamber to connect to these additional reservoirs. Typically, a cartridge can contain only a single liquid or reagent. In some embodiments, this may be a diluent that is used or required for various tests. There may also be multiple reservoirs that can each be connected to a conduit accessible to the pumping chamber conduit at a particular rotary position of the rotary valve.

For example, for many clinical trials there may be two reservoirs and for immunoassays there may be two or three different fluids within different reservoirs. In some variations of these embodiments, the cartridge may have multiple pump units, each of the pump units being connected to one or more reservoirs via its rotary valve. In this way, the immunoassays are dispensed using separate pump units and are not mixed by the pump procedure.

In another embodiment, the cartridge also contains a return conduit connected to the reservoir. The pumping chamber conduit can be operated to receive liquid from a first part of the reservoir. The return conduit can be operated to return liquid to a second part of the reservoir. The rotary valve can be further operated to rotate the pumping chamber conduit to connect to the return conduit. This embodiment can be beneficial because, for example, it can reduce the effect of gas bubbles that potentially occur when liquid is returned to the reservoir. This embodiment may further have the benefit of reducing the number of bubbles within the first part of the reservoir by transmitting the bubbles to the second part of the reservoir.

For example, liquid could be withdrawn from the reservoir when the rotary valve is turned so that the pump chamber conduit is in alignment with the reservoir conduit. After a certain amount of the liquid has been distributed through the outlet conduit, the rotary valve could be turned into such a position so that the pump chamber conduit is in alignment with the return conduit. The reservoir conduit can withdraw liquid from one part of the reservoir and the return conduit is used to return the liquid to a different part of the reservoir. For example, the two locations of the reservoir conduit and the return conduit could be far enough apart that it is unlikely that bubbles entering the reservoir through the return conduit will be withdrawn into the reservoir conduit when liquid is withdrawn from the reservoir. reservoir to pumping chamber.

In another embodiment, the cartridge further comprises a secondary reservoir. The cartridge further comprises a secondary reservoir conduit. The rotary valve can be further operated to rotate the pumping chamber conduit to connect to the secondary reservoir conduit. This embodiment can be beneficial in that it can enable a second or different liquid to be stored and dispensed using the cartridge, it can also enable the wasted liquid to be disposed of in the secondary reservoir.

It should be noted that additional tanks can be added to the cartridge by adding a third tank and a third tank line, a fourth tank and a fourth tank line, and so on, so that any number of tanks and tank lines can be added to the cartridge.

In another embodiment, the cartridge further comprises a connection conduit. The connecting conduit can be operated to transport liquid between the secondary tank and the tank. This embodiment can be beneficial because the connecting conduit can enable the secondary tank to be used as a place to deposit liquid to return it to the tank.

In another embodiment, the cartridge comprises a membrane that blocks the connection conduit. The membrane is permeable to liquid. This embodiment can be beneficial in that it can provide a means to filter liquid or block gas bubbles when liquid is returned from the secondary reservoir to the reservoir.

In another embodiment, the secondary reservoir comprises a bubble guiding structure. A structure Bubble guiding as used herein encompasses a structure that is used to guide a gas bubble to a predetermined location in a reservoir or to a vent. In some implementations, the bubble guiding structure can allow liquid to pass around the bubble as it moves through the reservoir. For example, a bubble structure can be a set of edges that are used to position and guide a bubble. The structures and edges can be spaced close enough to each other so that the surface tension of the liquid prevents the bubble from moving into regions that allow the liquid to surround the bubble. This can be beneficial because if the bubble is not properly confined, the bubble can become trapped in a particular position in the secondary reservoir and is not allowed to go to the top of the secondary reservoir or in the event that there is a passageway. connection to allow liquid to return to reservoir.

In another embodiment, the tank and / or the secondary tank comprise a vent. A vent as used herein is a structure that allows air bubbles or other volumes of gas to enter or leave the cartridge. Alternatively, the tank comprises such a vent or both the tank and the second tank comprise said vents.

In another embodiment, the vent is covered or sealed with a filter. The filter can be operated to seal the liquid in the cartridge. The filter can be hydrophobic in some embodiments. In some embodiments, the gas filter may have micropores to allow only gas to pass through, but no liquid. In some embodiments, the filter may be, but is not limited to: a porous form of polytetrafluoroethylene, carbon fibers, PTFE-coated carbon fibers, carbon nanotubes, polymer fibers, or fluoropolymer fibers.

In another embodiment, the liquid comprises magnetic microspheres.

In another embodiment, the liquid comprises latex microspheres.

In another embodiment, the liquid comprises a blood group determination reagent

In another embodiment, the liquid comprises an immune reagent.

In another embodiment, the liquid comprises an antibody.

In another embodiment, the liquid comprises an enzyme.

In another embodiment, the liquid comprises a recombinant protein.

In another embodiment, the liquid comprises an isolated viral strain.

In another embodiment, the liquid comprises a virus.

In another embodiment, the liquid comprises a biological reagent.

In another embodiment, the liquid comprises a solvent.

In another embodiment, the liquid comprises a diluent.

In another embodiment, the liquid comprises a dispersion.

In another embodiment, the liquid comprises nanoparticles.

In another embodiment, the liquid comprises a protein.

In another embodiment, the liquid comprises a salt.

In another embodiment, the liquid comprises a detergent.

In another embodiment, the liquid comprises a nucleic acid.

In another embodiment, the liquid comprises an acid.

In another embodiment, the liquid comprises a base.

In another embodiment, the liquid may comprise a suspension of particles, a liquid reagent, a liquid adhesive, a liquid food product, a liquid metal (eg, a solder) and / or any other liquid.

In another embodiment, the cartridge further comprises a sensor operable to measure liquid dispensed through the outlet conduit. For example, this sensor can be a capacitive or an optical sensor.

In another embodiment, the cartridge further comprises a coupling assembly for assembling the rotary valve and plunger to an actuator assembly. This embodiment can be beneficial in that it can enable the rotary valve and plunger to be conveniently connected to an actuator. The coupling assembly in some embodiments may enable the rotary valve and plunger to be actuated independently by the actuator assembly.

In some embodiments, it may be possible to have a cartridge with its own actuator. In this case, the cartridge further comprises an actuator. In some cases, the actuator can be connected to the coupling assembly or the actuator can be designed or operated to directly actuate the rotary valve and plunger independently.

A pump unit as used herein encompasses the rotary valve and plunger for pumping the liquid. When installed in an automated analyzer, there may be one actuator per pump unit or there may be one actuator that moves and is used to drive all cartridges within the automated analyzer. In this case, there may be a mechanism to move the relative positions between the cartridge and the single actuator. There may also be an actuator for a group of cartridges.

For example, there may be different configurations for the cartridge. In some embodiments, the cartridge may have a single pump unit. This single pump unit can have lines connected to different tanks. This can enable the cartridge to pump different types of liquids from the same cartridge. In another example, the cartridge may have multiple pump units, each of the pump units being connected to one or more reservoirs via its rotary valve.

In some embodiments, the cartridge comprises a pump unit and an assembled reservoir. This embodiment can be beneficial, because a universal pump unit can be created and tanks assembled to it when necessary. This can make it easier to have a greater variety of fluids available. You can also select tanks of different volumes. Different pump units can also be selected. Said different pump units, for example, can have pistons with a different stroke and / or diameter. This can affect the volume of the pump unit. In some applications, it may be desirable to pump a larger volume with greater accuracy and in other applications a smaller, but more accurate, pump volume may be desired. Thus, the use of a pumping unit and an assembled tank allows a modular concept that allows combining tanks comprising different types and / or volumes of liquids with a pumping unit that is optimized to distribute a defined volume of this liquid. This modular concept makes it possible to provide a large set of optimized cartridges based on a small set of pumping units and / or reservoirs that can be combined in different modes. The assembly of the pump unit and the buildable tank can be done at the factory site as a manufacturing step during the production of cartridges or at the user's site, for example, by mounting the pump unit with the buildable tank before inserting the cartridge into an automated analyzer.

In another embodiment, the rotary valve comprises a cylindrical part. The pumping chamber is a cavity within the rotary valve. The pumping chamber is formed by the cavity and the plunger. The cartridge comprises a cartridge body with a cylindrical space to receive the cylindrical part. The rotary valve can be operated to rotate within the cylindrical space.

In another embodiment, the reservoir conduit and the outlet conduit are located in the cylindrical space. The pumping chamber conduit is located in the cylindrical part.

In another embodiment, the cartridge comprises multiple pump units.

In another embodiment, the cartridge comprises multiple reservoirs.

In another embodiment, the multiple reservoirs are filled with different liquids.

In another aspect, the invention provides an automated analyzer for analyzing a biological sample. The automated system can be operated to contain a cartridge in accordance with one embodiment of the invention. The automatic analyzer comprises an operable actuator assembly for actuation of the plunger and valve. The automatic analyzer further comprises a controller (520, 1920) to control the operation of the actuator assembly.

In another aspect, an automatic analyzer is provided to contain a cartridge. An automated analyzer as used herein encompasses a system for automatically analyzing a biological sample. The automatic analyzer comprises an actuator assembly operable for actuation linear piston and for rotary actuation of the rotary valve. The actuator assembly can be further operated to actuate the plunger and the rotary valve independently. The automatic analyzer further comprises a controller for controlling the operation of the actuator assembly.

In some embodiments, the automated analyzer can be adapted to hold multiple cartridges in accordance with one embodiment of the invention. In this case, there may be a mechanism to provide relative movement between the cartridges and a reaction tube / cuvette. There may be one actuator per pump unit or there may be one actuator used for multiple cartridges. In this case, there may be a mechanism or a robotic system to provide relative movement between the cartridge and the actuator. There may also be embodiments where there are multiple actuators, each used for a group of cartridges. The cartridge group could be predetermined or the cartridge group could be determined on the fly. Alternatively, multiple actuators can be used for a cartridge or a group of cartridges, for example, for different purposes such as predistribution or postdistribution actions.

In another embodiment, the automatic analyzer comprises the cartridge.

In another embodiment, the controller can be operated to control the actuator assembly to rotate the pump chamber conduit to connect with the reservoir conduit by rotating the rotary valve. The controller can be further operated to control the actuator assembly to fill the pump chamber by increasing the volume of the pump chamber with the plunger. The controller can be further operated to control the actuator assembly to rotate the pumping chamber conduit to connect with the outlet conduit by rotating the rotary valve. The controller can be further operated to control the actuator assembly to pump the liquid through the outlet conduit by decreasing the volume of the pumping chamber with the plunger. This embodiment can be beneficial in that it provides a method of pumping liquid through the outlet conduit.

In another embodiment, the controller can be operated to control the actuator assembly to receive liquid from the outlet conduit by increasing the volume of the pump chamber with the plunger.

In another embodiment, the controller can be operated to control the actuator assembly to rotate the pump chamber conduit to connect with the reservoir conduit by rotating the rotary valve. The controller can be further operated to control the actuator assembly to return liquid to the reservoir by decreasing the volume of the pump chamber with the plunger. This embodiment can be advantageous because it allows the pump to operate without priming. You can use 100% or almost 100% of the liquid.

In another embodiment, the controller can be operated to control the actuator assembly to rotate the pump chamber conduit to connect with the reservoir conduit by rotating the rotary valve. The controller can be further operated to control the actuator assembly to mix the liquid in the reservoir by repeatedly increasing and decreasing the volume of the pumping chamber with the plunger. In the event that the liquid contains microspheres or particles such as magnetic or latex microspheres, this embodiment can be used to mix the liquid and its compounds.

In another embodiment, the cartridge comprises an outlet nozzle. The automatic analyzer further comprises a meniscus detector for detecting a meniscus of the liquid. The controller can be operated to control the actuator to force liquid through the outlet nozzle. The controller can be further operated to detect the meniscus using the meniscus detector. The controller can be further operated to control the actuator to stop liquid from being forced through the outlet when the meniscus is at a predetermined location. This embodiment can be beneficial in that it can enable a more accurate and precise distribution of the liquid. This embodiment can be beneficial because if the meniscus is in the same place when the liquid distribution begins, then the liquid distribution can be more exact, more precise and / or more reproducible. The meniscus can be on the inside or outside of the outlet nozzle. For example, the outlet nozzle may be a long tube-like structure and the meniscus may have a particular position within the tube. In other embodiments, the meniscus can be formed by a drop of the liquid that is suspended from the outlet nozzle. In many applications, the meniscus is preferably located right at the orifice of the outlet nozzle.

In another embodiment, the controller can be further operated to control the actuator to force a predetermined volume of liquid through the outlet. In some embodiments, the actuator can be controlled to force the predetermined volume of liquid through the outlet nozzle after the meniscus is at the predetermined location.

In another embodiment, the meniscus detector is any one of the following: a capacitive sensor, an optical sensor, and a camera. When the meniscus is inside the mouthpiece, a capacitive sensor can be used to detect the location of the meniscus. In case the mouthpiece is optically transparent, an optical sensor can also be used to determine the location of the meniscus within the mouthpiece. If the meniscus extends further Beyond the nozzle, then each of a capacitive sensor, an optical sensor, or a camera can be used to determine the location of the meniscus.

In another embodiment, the automated analyzer can be operated to hold multiple cartridges. Each of the multiple cartridges is in accordance with an embodiment of the invention.

In another embodiment, the automated analyzer further comprises the multiple cartridges.

The multi-cartridge embodiment can be implemented in a variety of modes. For example, each pump unit can have its own actuator assembly. This can be a parallel operation. In another example, the cartridges can be moved and positioned on the same actuator assembly or an actuator assembly can be moved between different cartridges or even between different pump units that are part of the same cartridge. In still other embodiments, there may be multiple actuators and the cartridges are moved by a robotic mechanical system between these multiple actuators.

In another embodiment, the automatic analyzer comprises a sensor or meter system operable to measure the distribution of the liquid. The controller can be operated to control the distribution of the liquid in accordance with measurements or data received from the sensor or meter system. In other words, the controller can be operated to form a closed-loop control system with the sensor or measurement system to control the distribution of the liquid.

In another aspect, a method of operating a cartridge is provided. The procedure comprises the stages of:

rotating the rotary valve to rotate the pumping chamber conduit to connect with the reservoir conduit; increasing the volume of the pumping chamber with the plunger to fill the pumping chamber; rotating the rotary valve to rotate the pumping chamber conduit to connect with the outlet conduit; decrease the volume of the pumping chamber with the plunger to pump the liquid through the outlet conduit.

In another embodiment, the method further comprises the step of increasing the volume of the pumping chamber with the plunger to recover the liquid from the outlet conduit.

In another embodiment, the method further comprises the steps of: turning the rotary valve to turn the pumping chamber conduit to connect with the reservoir conduit; and decreasing the volume of the pumping chamber with the plunger to return the liquid to the reservoir.

In another embodiment, the method further comprises the steps of: turning the rotary valve to turn the pumping chamber conduit to connect with the reservoir conduit; and repeatedly increasing and decreasing the volume of the pumping chamber with the plunger to mix the liquid in the reservoir.

In one aspect, the invention provides a cartridge for dispensing liquid. The cartridge comprises a slide valve. The slide valve has a rectilinear motion. The slide valve can also be called a rectilinear valve. The slide valve comprises a pumping chamber for pumping the liquid. The slide valve can be operated to translate a pumping chamber conduit. The pump chamber conduit connects to the pump chamber. The cartridge further comprises a plunger operable to change the volume of the pump chamber. The cartridge further comprises a reservoir for storing the liquid. The cartridge further comprises a reservoir conduit for connecting the reservoir with the slide valve. The slide valve can be operated to translate the pumping chamber conduit to connect with the reservoir conduit. The cartridge further comprises an outlet conduit to distribute the liquid. The slide valve can be further operated to translate the pumping chamber conduit to connect with the outlet conduit. This embodiment can be beneficial in that the combination of the slide valve and the plunger allow exact distribution of the liquid. Furthermore, the embodiment can also enable a reduced amount of wasted liquid produced when liquid is dispensed through the cartridge.

The embodiments can also have the advantage that a large set of pumping actions is possible by the pumping chamber. This embodiment can have the advantage that a wide variety of pumping actions can be performed with the pumping chamber by controlling the translational position of the slide valve and properly operating the plunger. For example, the slide valve can be positioned so that the pump chamber conduit connects to the reservoir conduit. In this case, the plunger can be used to draw liquid from the reservoir to the pumping chamber or it can be used to pump the liquid from the pumping chamber back to the reservoir.

The present embodiment can enable other types of actions using the pumping chamber. For example, when the pump chamber conduit is aligned or connected with the reservoir conduit, the plunger can be used repeatedly to increase and decrease the volume of the pump chamber. This can make it possible to mix the liquid inside the reservoir. Additionally, the ability to return liquid to the reservoir can reduce the amount of liquid that is wasted.

This embodiment can also enable a so-called low-waste priming or no-waste priming function of the pumping chamber, whereby nothing or possibly only a very small amount of the liquid is wasted or discarded when liquid is pumped out through. outlet duct. For example, when the pump chamber conduit connects to the outlet conduit, the plunger can be used to decrease the volume of the pump chamber and thereby force or distribute liquid out through the outlet conduit. During the procedure of doing this, there may be liquid within the outlet conduit that does not exit the outlet conduit. After the correct amount of liquid has been dispensed, the plunger can then be used to increase the volume of the pump chamber, thereby removing liquid that may remain within the outlet conduit back into the pump chamber. pumping. Liquid could then be contained within the pumping chamber or, if the slide valve is translated in alignment with the reservoir conduit, the liquid that was previously within the outlet conduit can be pumped back into the reservoir.

The slide valve can also provide a means to prevent liquid from accidentally escaping from the reservoir. For example, the slide valve can be translated in some embodiments to a position where it does not align with the outlet conduit or the reservoir conduit. This can prevent liquid and / or gas from exiting the outlet conduit and / or liquid and / or gas in a reservoir from escaping or draining into the pumping chamber.

In some embodiments, the cartridge comprises a pump unit and an assembled reservoir. This embodiment can be beneficial, because a universal pump unit can be created and tanks assembled to it when necessary. This can make it easier to have a greater variety of fluids available. You can also select tanks of different volumes. Different pump units can also be selected. Said different pump units, for example, can have pistons with a different stroke and / or diameter. This can affect the volume of the pump unit. In some applications, it may be desirable to pump a larger volume with greater accuracy and in other applications a smaller, but more accurate, pump volume may be desired.

The use of a pumping unit and an assembled tank can make it possible to make a modular system that allows the combination of tanks comprising different types and / or volumes of liquids with a pumping unit that is optimized to distribute a defined volume of this liquid. This modular system can provide a large set of optimized cartridges based on a small set of pumping units and / or reservoirs that can be combined in different modes. The assembly of the pump unit and the buildable tank can be done at the factory site as a manufacturing step during the production of cartridges or at the user's site, for example, by mounting the pump unit with the buildable tank before inserting the cartridge into an automated analyzer.

The tank can be built in a variety of ways. In some embodiments, the reservoir may be a hard-walled chamber, preferably made of plastics using injection molding or thermoforming processes. In some embodiments, the reservoir can be a chamber with a flexible wall. In some embodiments, the reservoir could be a bag or sack. In other embodiments, the reservoir could be a bag or sack supported by an outer container. In other embodiments, the reservoir could be a tube.

In some embodiments, the pump chamber conduit is aligned with the reservoir conduit and / or outlet conduit using mechanical stops. As an alternative to the use of mechanical stops, alignment can also be achieved by other means. For example, by spatially defined changes of physical or geometric properties, for example, by changes in coefficients of friction or diameter. In other embodiments, no mechanical stops are used and alignment is done by an actuator system that is assembled to the cartridge during use.

In another embodiment, the cartridge further comprises an outlet nozzle connected to the outlet conduit. An outlet nozzle as used herein includes a nozzle design to minimize liquid waste and can enable drops to fall cleanly during the dosing procedure. For example, in a simple tube, a drop of the liquid can be suspended on the outside of the nozzle after the plunger is used to decrease the volume of the pump chamber. The shape or function of the outlet nozzle can be designed to reduce the chances that a drop of the liquid will become suspended from it. For example, the outlet nozzle may have a so-called duckbill conformation and be a duckbill nozzle.

In other embodiments, the cartridge may have additional reservoirs and additional reservoir lines that enable the pump chamber to connect to these additional reservoirs. Typically, a cartridge can contain only a single liquid or reagent. In some embodiments, this may be a diluent that is used or required for various tests. There may also be multiple reservoirs that can each be connected to a conduit accessible to the pumping chamber conduit at a particular rectilinear position of the slide valve.

For example, for many clinical trials there may be two reservoirs and for immunoassays there may be two or three different fluids within different reservoirs. In some variations of these embodiments, the cartridge may have multiple pump units, each of the pump units being connected to one or more reservoirs via its slide valve. In this way, the immunoassays are dispensed using separate pump units and are not mixed by the pump procedure.

In some embodiments, the slide valve and plunger can be operated to actuate independently. In other embodiments, the plunger or plunger drive is also used to drive the slide valve.

In another embodiment, the cartridge further comprises a return conduit connected to the reservoir. The pumping chamber conduit can be operated to receive liquid from a first part of the reservoir. The return conduit can be operated to return liquid to a second part of the reservoir. The slide valve can be further operated to translate the pumping chamber conduit to connect to the return conduit. This embodiment may have the benefit of reducing the number of bubbles within the first part of the reservoir by transmitting the bubbles to the second part of the reservoir.

For example, liquid could be withdrawn from the reservoir when the slide valve is translated so that the pump chamber conduit is in alignment with the reservoir conduit. After a certain amount of the liquid has been distributed through the outlet conduit, the slide valve could be translated into such a position so that the pumping chamber conduit is in alignment with the return conduit. The reservoir conduit can withdraw liquid from one part of the reservoir and the return conduit is used to return the liquid to a different part of the reservoir. For example, the two locations of the reservoir conduit and the return conduit could be far enough apart that it is unlikely that bubbles entering the reservoir through the return conduit will be withdrawn into the reservoir conduit when liquid is withdrawn from the reservoir. reservoir to pumping chamber.

In another embodiment, the cartridge further comprises a secondary reservoir. The cartridge further comprises a secondary reservoir conduit. The slide valve can be further operated to translate the pumping chamber conduit to connect to the secondary reservoir conduit. This embodiment can be beneficial in that it can enable a second or different liquid to be stored and dispensed using the cartridge, it can also enable the wasted liquid to be disposed of in the secondary reservoir.

In another embodiment, the secondary tank comprises a vent. A vent as used herein is a structure that allows air bubbles or other volumes of gas to enter or leave the cartridge. Alternatively, the tank comprises such a vent or both the tank and the secondary tank comprise said vents.

It should be noted that additional tanks can be added to the cartridge by adding a third tank and a third tank line, a fourth tank and a fourth tank line, and so on, so that any number of tanks and tank lines can be added to the cartridge. Additional reservoirs can also comprise vents.

In another embodiment, the cartridge further comprises a connection conduit. The connecting conduit can be operated to transport liquid between the secondary tank and the tank. This embodiment can be beneficial because the connecting conduit can enable the secondary tank to be used as a place to deposit liquid to return it to the tank.

In another embodiment, the cartridge comprises a membrane or grid or filter located within the connecting conduit. If a membrane is used, the membrane is permeable to liquid. Such membranes are described, for example, in "Unimpeded Permeation of Water Through Helium-Leak-Tight Graphene-Based Membranes" (RR Nair et al .; Science 335, 442 (2012). If a mechanical screen or filter is used, the Mesh or hole size has to be smaller than the gas bubble size to prevent gas bubbles from passing through the screen or filter. This embodiment can be beneficial because it can provide a means to filter liquid or block gas bubbles when liquid is returned from the secondary reservoir to the reservoir.

In another embodiment, the secondary reservoir comprises a bubble guiding structure. A bubble guiding structure as used herein encompasses a structure that is used to guide a gas bubble to a predetermined location in a reservoir or to a vent. In some implementations, the bubble guiding structure can allow liquid to pass around the bubble as it moves through the reservoir. For example, a bubble structure can be a set of edges that are used to position and guide a bubble. The structures and edges can be spaced close enough to each other so that the surface tension of the liquid prevents the bubble from moving into regions that allow the liquid to surround the bubble. This can be beneficial because if the bubble is not properly confined, the bubble can become trapped in a particular position in the secondary reservoir and is not allowed to go to the part. top of the secondary tank or if there is a connection pipe to allow liquid to return to the tank.

In another embodiment, the tank and / or the secondary tank comprises a vent. The vent is sealed with a filter. The filter is permeable to air. The filter can be operated to seal the liquid in the cartridge. The filter can be hydrophobic in some embodiments. In some embodiments, the gas filter may have micropores to allow only gas to pass through, but no liquid. In some embodiments, the filter may be, but is not limited to: a porous form of polytetrafluoroethylene, carbon fibers, PTFE-coated carbon fibers, carbon nanotubes, polymer fibers, or fluoropolymer fibers.

In another embodiment, the liquid comprises magnetic microspheres.

In another embodiment, the liquid comprises latex microspheres.

In another embodiment, the liquid comprises a blood group determination reagent

In another embodiment, the liquid comprises an immune reagent.

In another embodiment, the liquid comprises an antibody.

In another embodiment, the liquid comprises an enzyme.

In another embodiment, the liquid comprises a recombinant protein.

In another embodiment, the liquid comprises an isolated viral strain.

In another embodiment, the liquid comprises a virus.

In another embodiment, the liquid comprises a biological reagent.

In another embodiment, the liquid comprises a solvent.

In another embodiment, the liquid comprises a diluent.

In another embodiment, the liquid comprises a dispersion.

In another embodiment, the liquid comprises nanoparticles.

In another embodiment, the liquid comprises a protein.

In another embodiment, the liquid comprises a salt.

In another embodiment, the liquid comprises a detergent.

In another embodiment, the liquid comprises a nucleic acid.

In another embodiment, the liquid comprises an acid.

In another embodiment, the liquid comprises a base.

In other embodiments, the liquid is a suspension of particles, a liquid reagent, a liquid adhesive, a liquid food product, a liquid metal (eg, a solder), or any other liquid.

In another embodiment, the cartridge further comprises a sensor operable to measure liquid dispensed from the outlet nozzle. For example, this sensor can be a capacitive or an optical sensor.

In another embodiment, the cartridge further comprises a coupling assembly for assembling the slide valve and plunger to an actuator assembly. In some embodiments, the coupling assembly is only assembled to the plunger. In other embodiments, the coupling assembly is assembled to both the slide valve and the plunger so that they can be actuated independently.

In some embodiments, it may be possible to have a cartridge with its own actuator. In this case, the cartridge further comprises an actuator. In some cases, the actuator can be connected to the coupling assembly or the actuator can be designed or operated to directly actuate the slide valve and plunger independently.

A pump unit as used here encompasses the slide valve and plunger to pump the liquid. When installed in an automated analyzer, there may be one actuator per pump unit or there may be one actuator that moves and is used to drive all cartridges within the automated analyzer. In this case, there may be a mechanism to move the relative positions between the cartridge and the single actuator. There may also be an actuator for a group of cartridges.

For example, there may be different configurations for the cartridge. In some embodiments, the cartridge may have a single pump unit. This single pump unit can have lines connected to different tanks. This can enable the cartridge to pump different types of liquids from the same cartridge. In another example, the cartridge may have multiple pump units, each of the pump units being connected to one or more reservoirs via its slide valve.

In another embodiment, the cartridge comprises multiple pump units.

In another embodiment, the cartridge comprises multiple reservoirs.

In another embodiment, the multiple reservoirs are filled with different liquids.

In another embodiment, the slide valve comprises a piston. The pumping chamber is a cavity within the piston. The pumping chamber is formed by the cavity and the plunger. The piston can be operated for its translation movement within the volume.

The piston and the volume can have different cross-sectional shapes that correspond to each other. For example, both the piston and the corresponding volume can have a round, oval or other cross-sectional shape.

In another embodiment, the piston and slide valve can be actuated for collinear movement. In other words, the piston and the slide valve can be operated to have translational movement that is parallel or in the same direction.

In another embodiment, the slide valve comprises a reservoir conduit mechanical stop for aligning the pumping chamber conduit with the reserve conduit. In other words, there is a mechanical stop that aligns the piston so that the pump chamber conduit aligns with the reservoir conduit.

In another embodiment, the slide valve comprises an outlet conduit mechanical stop for aligning the pumping chamber conduit with the outlet conduit. In other words, the slide valve has a mechanical stop that aligns the piston so that the pump chamber passage is in line with the outlet passage.

In another embodiment, the piston comprises two mechanical piston stops to limit the movement of the piston relative to the piston. The plunger can be operated to actuate the piston. This embodiment can be beneficial in that it enables the cartridge to be operated with a single linear actuator. This is true, in particular, when there are the combined embodiments of also having a reservoir conduit mechanical stop and an outlet conduit mechanical stop.

In another aspect, the invention provides an automated analyzer for analyzing the biological sample. The automated analyzer can be operated to contain a cartridge in accordance with one embodiment of the invention. The automatic analyzer comprises an operable actuator assembly for linear actuation of the plunger and slide valve.

The actuator assembly may have one or two actuators, depending on the design of the cartridge. For example, in some embodiments, the linear actuator can only drive the plunger. In other embodiments, there may be a linear actuator that drives the slide valve and plunger independently. The automatic analyzer further comprises a controller for controlling the operation of the actuator assembly. In another embodiment, the automatic analyzer comprises the cartridge.

In another embodiment, the automated analyzer may be operated to contain a cartridge in accordance with one embodiment. The piston comprises two mechanical piston stops to limit the movement of the piston relative to the piston and where the piston can be operated to actuate the piston. The actuator assembly can be operated for linear drive of the plunger. This embodiment can be beneficial in that only a single linear actuator is used.

The slide valve is actuated through or by the piston.

In another embodiment, the actuator assembly can be operated for linear actuation. separate from the piston and for linear actuating of the slide valve. In this embodiment, there are two linear actuators in the actuator assembly and the plunger and slide valve are actuated independently. This embodiment can be beneficial because it enables more complex pump behaviors or protocols by the automated analyzer.

In another embodiment, the controller can be operated to control the actuator assembly to translate the pumping chamber conduit to connect with the reservoir conduit by translating the slide valve. The controller can be further operated to control the actuator assembly to fill the pump chamber by increasing the volume of the pump chamber with a plunger. The controller can be further operated to control the actuator assembly to translate the pumping chamber conduit to connect with the outlet conduit by translating the slide valve. The controller can be further operated to control the actuator assembly to pump the liquid through the outlet conduit by decreasing the volume of the pumping chamber with the plunger.

Translating the slide valve is equivalent herein to translating the piston in embodiments where the slide valve has a piston.

In another embodiment, the controller can be operated to control the actuator assembly to translate the pumping chamber conduit to connect with the reservoir conduit by translating the slide valve. The controller can be further operated to control the actuator assembly to return liquid to the reservoir by decreasing the volume of the pump chamber with a plunger. This embodiment can be advantageous because it allows the pump to operate without priming. You can use 100% or almost 100% of the liquid.

In another embodiment, the controller can be operated to control the actuator assembly to translate the pumping chamber conduit to connect with the reservoir conduit by translating the slide valve. The controller can be further operated to control the actuator assembly to mix the liquid in the reservoir by repeatedly increasing and decreasing the volume of the pumping chamber with the plunger. In the event that the liquid contains microspheres or particles such as magnetic or latex microspheres, this embodiment can be used to mix the liquid and its compounds.

In another embodiment, the controller can be further operated to control the actuator assembly to recover liquid from the outlet conduit by increasing the volume of the pump chamber with the plunger.

In another embodiment, the cartridge comprises an outlet nozzle. The automatic analyzer further comprises a meniscus detector to detect the meniscus of the liquid. The controller can be further operated to control the actuator assembly to force liquid through the outlet nozzle. The controller can be further operated to detect the meniscus using the meniscus detector. The controller can be further operated to control the actuator to stop liquid from being forced through the outlet when the meniscus is at a predetermined location. This embodiment can be beneficial in that it can enable a more accurate and precise distribution of the liquid. This embodiment can be beneficial because if the meniscus is in the same place when the liquid distribution begins, then the liquid distribution can be more exact, more precise and / or more reproducible. The meniscus can be on the inside or outside of the outlet nozzle.

For example, the outlet nozzle may be a long tube-like structure and the meniscus may have a particular position within the tube. In other embodiments, the meniscus can be formed by a drop of the liquid that is suspended from the outlet nozzle. In many applications, the meniscus is preferably located right at the orifice of the outlet nozzle.

In another embodiment, the controller can be further operated to control the actuator to force a predetermined volume of liquid through the outlet. In some embodiments, the actuator can be controlled to force the predetermined volume of liquid through the outlet nozzle after the meniscus is at the predetermined location.

In another embodiment, the meniscus detector is any one of the following: a capacitive sensor, an optical sensor, and a camera. When the meniscus is inside the mouthpiece, a capacitive sensor can be used to detect the location of the meniscus. In case the mouthpiece is optically transparent, an optical sensor can also be used to determine the location of the meniscus within the mouthpiece. If the meniscus extends beyond the nozzle, then each of a capacitive sensor, an optical sensor, or a camera can be used to determine the location of the meniscus.

In another embodiment, the automated analyzer can be operated to hold multiple cartridges. Each of the multiple cartridges is in accordance with an embodiment of the invention.

In another embodiment, the automated analyzer further comprises the multiple cartridges.

The multi-cartridge embodiment can be implemented in a variety of modes. For example, each pump unit can have its own actuator assembly. This can be a parallel operation. In another example, the cartridges can be moved and positioned on the same actuator assembly or an actuator assembly can be moved between different cartridges or even between different pump units that are part of the same cartridge. In still other embodiments, there may be multiple actuators and the cartridges are moved by a robotic mechanical system between these multiple actuators.

In another embodiment, the automated analyzer can be operated to hold multiple cartridges. Each of the multiple cartridges is in accordance with an embodiment of the invention. In this case, there may be a mechanism to provide relative movement between the cartridges and a reaction tube / cuvette. There may be one actuator per pump unit or there may be one actuator used for multiple cartridges. In this case, there may be a mechanism or a robotic system to provide relative movement between the cartridge and the actuator. There may also be embodiments where there are multiple actuators, each used for a group of cartridges. The cartridge group could be predetermined or the cartridge group could be determined on the fly. Alternatively, multiple actuators can be used for a cartridge or a group of cartridges, for example, for different purposes such as predistribution or postdistribution actions.

In another embodiment, the automatic analyzer comprises a sensor or meter system operable to measure the distribution of the liquid. The controller can be operated to control the distribution of the liquid in accordance with measurements or data received from the sensor or meter system. In other words, the controller can be operated to form a closed loop control system with the sensor or meter system to control the distribution of the liquid.

In another aspect, the invention provides a method of operating the cartridge in accordance with an embodiment of the invention. The method comprises the step of translating the slide valve to translate the pumping chamber conduit to connect with the reservoir conduit. The method further comprises the step of increasing the volume of the pump chamber with the plunger to fill the pump chamber. The method further comprises the step of translating the slide valve to translate the pumping chamber conduit to connect with the outer outlet conduit. The method further comprises the step of decreasing the volume of the pump chamber with the plunger to pump the liquid through the outlet conduit.

Descriptive embodiments of an automated analyzer may also be applicable to an automated system for dispensing liquids.

In another aspect, the invention provides an automatic system for dispensing liquids. The automated system can be operated to contain a cartridge in accordance with one embodiment of the invention. The automatic system comprises an actuator assembly (200, 400, 904, 904 ', 904 ") operable for linear actuation of the plunger and slide valve. The automatic system further comprises a controller (920) to control the operation of the actuator assembly.

In another embodiment, the actuator assembly can be operated for linear actuation of the plunger.

In another embodiment, the automatic system can be operated for separate linear actuation of the plunger and for linear actuation of the slide valve.

In another embodiment, the cartridge comprises an outlet nozzle (126). The automatic analyzer further comprises a meniscus detector (1002, 1002 ', 1002 ") to detect a meniscus of the liquid. The controller can be operated to: control the actuator assembly to force liquid through the outlet nozzle; detect the meniscus using the meniscus detector, and controlling the actuator to stop liquid from being forced through the outlet when the meniscus is at a predetermined location.

It is understood that one or more claims and / or embodiments can be combined as long as the combined elements are not mutually exclusive.

Brief description of the drawings

In the following, embodiments of the invention are explained in greater detail, by way of example only, with reference to the drawings, in which:

fig. 1 illustrates a cartridge and actuator assembly in accordance with one embodiment;

fig. 2 illustrates how the cartridge can be used to pump liquid through the outlet conduit;

fig. 3 illustrates a pumping procedure similar to that shown in FIG. 2, except that stages are performed additional to remove liquid from the outlet conduit;

fig. 4A and 4B illustrate how liquid can be pumped through the outlet conduit where liquid is taken from the reservoir and then excess liquid is pumped from the outlet nozzle and outlet conduit to the secondary reservoir;

a fig. 5 illustrates an automatic analyzer in accordance with one embodiment;

a fig. 6 illustrates a bubble guide in accordance with one embodiment of the invention;

a fig. 7 illustrates an automatic analyzer according to another embodiment;

a fig. 8A, 8B, 8C and 8D illustrate the operation of a cartridge using a meniscus detector;

a fig. 9 illustrates the correlation of target volume and measured volume for one embodiment of a rotary valve;

a fig. 10 shows a curve indicating the accuracy and the coefficient of variation for the distribution of liquids of different viscosities and surface tensions by an embodiment of a rotary valve;

a fig. 11 shows a cartridge according to one embodiment;

a fig. 12 shows the cartridge of fig. 1 connected to an actuator assembly;

a fig. 13A shows a cartridge according to another embodiment;

a fig. 13B shows a cartridge according to another embodiment;

a fig. 14 shows the cartridge of fig. 2 connected to an actuator assembly;

a fig. 15A and 15B show views in different phases of the slide valve and plunger of the embodiment shown in fig. 1;

a fig. 16A and 16B illustrate a slide valve and piston combination in accordance with another embodiment; a fig. 17 shows two views of a slide valve and plunger combination according to another embodiment;

a fig. 18A and 18B illustrate one mode of operation of the slide valve and piston of the embodiment shown in FIG. 3;

a fig. 19 illustrates an automatic analyzer in accordance with one embodiment;

a fig. 20 illustrates an automatic analyzer according to another embodiment;

a fig. 21 shows a cartridge according to another embodiment;

a fig. 22 illustrates an alternative slide valve design;

a fig. 23 illustrates an alternative slide valve design;

a fig. 24 illustrates an alternative slide valve design;

a fig. 25 illustrates an alternative slide valve design;

a fig. 26 illustrates an alternative slide valve design; Y

a fig. 27 illustrates an alternative slide valve design.

Detailed description

Items similarly numbered in these figures are equivalent items or perform the same function. Items that have been previously analyzed will not necessarily be analyzed in later figures if the function is equivalent.

Fig. 1 illustrates a cartridge 100 and an actuator assembly 102 in accordance with one embodiment. Set Actuator 102 comprises a linear actuator 104 operable in direction 105. Actuator assembly 102 further comprises a rotary actuator 106 operable in direction 107.

The cartridge 100 comprises a plunger 108 and a rotary valve 110. The cartridge 100 comprises a cartridge body 112 having a cylindrical space 116. In this case, the cylindrical space 116 is formed by an antifriction metal. The rotary valve 110 has at least one cylindrical portion 114 adapted to fit into the cylindrical space 116 of the cartridge body 112. The rotary valve 110 has a hollow space that forms a pump chamber 118 that is formed by the hollow space and the plunger. 108. The pump chamber 118 has a pump chamber conduit 120 that is formed in a wall of the rotary valve 110. The rotary valve 110 can be operated to rotate within the cylindrical space 116 to locate the pump chamber conduit. 120 in different angular positions.

Cartridge 100 further comprises a reservoir 122 for filling with a liquid. Not shown in fig. 1, but cartridge 100 may also comprise a vent to allow gas to vent to reservoir 122. Cartridge 100 further comprises reservoir conduit 124. Reservoir conduit 124 provides reservoir 122 access to pump chamber conduit 120 when the pumping chamber duct is in the correct turning position. Cartridge 100 also comprises an optional outlet nozzle 126 for dispensing the liquid. Outlet nozzle 126 connects to outlet conduit 128. Outlet conduit 128 allows pump chamber 118 to distribute liquid. Outlet conduit 128 in this embodiment connects to outlet nozzle 126 when pump chamber conduit 120 is in the correct rotational position. Also shown is a coupling assembly 130 that couples actuator assembly 102 to cartridge 100. Coupling assembly 130 is designed to be and actuate piston 108 in the linear direction 105. Coupling assembly 130 is also adapted to be rotatable. independently of the rotary valve 110. For example, there may be slots cut out in the rotary valve 110 and there may be a shaping in the coupling assembly 130 that engages the groove of the rotary valve 110. The example shown in FIG. 1 is just one way that rotary valve 110 and piston 108 can be actuated. Other equivalent mechanisms can also be used to actuate and assemble rotary valve 110 and piston 108.

Fig. 2 illustrates four views 200, 202, 204, 206 of cartridge 100. FIG. 2 illustrates how cartridge 100 can be used to pump liquid through outlet conduit 128. In view 200, pump chamber conduit 120 is aligned with reservoir conduit 124. Plunger 108 is fully depressed and chamber pump 118 has no volume or is extremely small. In this example, plunger 108 is fully depressed. However, fully depressing plunger 108 is not a requirement for operation. In the examples described herein, it is the relative motion of the plunger that is relevant. For example, depressing the plunger 108 causes the volume of the pump chamber to decrease and this forces the liquid through the outlet conduit.

Then, in view 202, the plunger is withdrawn in direction 208. This causes liquid in reservoir 122 to enter pump chamber 118. Then, in view 204, rotary valve 110 rotates 210 so that the inlet conduit Pump chamber 120 is aligned with outlet conduit 128. Pump chamber 118 is now isolated from reservoir 122. Then, in view 206, plunger 108 is pushed in direction 212 and liquid 214 exits via outlet conduit. exit 128.

Fig. 3 illustrates a pumping procedure similar to that shown in FIG. 2, except that additional steps are taken to remove liquid from outlet nozzle 126 and outlet conduit 128. The same views 202, 204, and 206 are shown again. Three additional views 300, 302 and 304 of cartridge 100 are presented. The step according to view 300 is performed after view 206. Plunger 108 is withdrawn in direction 306 to draw liquid from outlet nozzle 126 into conduit outlet 128. In this example, plunger 108 is pulled out far enough so that a bubble 208 forms in pump chamber 118. Then, in view 302, rotary valve 110 is rotated in direction 310 so that the Pumping chamber conduit 120 is aligned with reservoir conduit 124. Finally, in view 304, plunger 108 is depressed in direction 312, thereby forcing liquid out of pumping chamber 118 into reservoir 122. Further , bubble 308 was also forced into reservoir 122.

Figs. 4A and 4B show seven views 400, 402, 404, 406, 408, 410, 412 of a different embodiment of a cartridge 414. In this embodiment, the cartridge 414 has a reservoir 122 and a secondary reservoir 416. The fig. 4 illustrates how liquid 214 can be pumped through outlet conduit 128 where liquid is taken from reservoir 122 and then excess liquid is pumped from outlet nozzle 126 and outlet conduit 128 to secondary reservoir 416. In From this cartridge 414 it can be seen that there is a connecting conduit 418 between the reservoir 122 and the secondary reservoir 416. The connecting conduit 418 is not necessarily present in all embodiments. In some alternative embodiments there is also a membrane that is permeable to liquid that can be arranged somewhere in connecting conduit 418. View 400 shows plunger 108 as being fully depressed and pump chamber conduit 120 as being fully depressed. is aligned with reservoir conduit 124. Then, in view 402, the plunger is pulled out 420, filling pump chamber 118 with liquid 214. Then, in view 404, rotary valve 110 is turned so that pump chamber conduit 120 is aligned with outlet conduit 128.

The rotary valve is rotated in direction 422. Then, in view 406, plunger 108 is pressed in direction 424 and liquid 214 is forced out of outlet conduit 128. Then, in view 408, plunger 108 is withdrawn into the direction 426 to draw liquid 214 that was previously in outlet conduit 128 and pump chamber conduit 120 back to pump chamber 118. Then, in view 410, a rotary valve 110 is turned in direction 428 to aligning pump chamber conduit 120 with secondary reservoir conduit 430. Finally, in view 412, plunger 108 is depressed in direction 432, which forces bubble 308 and liquid 126 into secondary chamber 416. In some In embodiments, the secondary chamber 416 may be vented to the atmosphere. In some embodiments, the vent may be covered with a filter that allows gas to pass through but prevents liquid 416 from leaking out of cartridge 414. In view 412, pump chamber conduit 120 and secondary reservoir conduit 430 are shown as being filled with bubble 308.

Fig. 5 illustrates an automated analyzer 500 in accordance with one embodiment. This automated analyzer is shown as having three cartridges 502, 502 'and 502 ". There is an actuator assembly 504 connected to cartridge 502. There is an actuator assembly 504' assembled to cartridge 502 '. There is an actuator assembly 504" assembled to cartridge 502 ". Actuator assemblies 504, 504 ', 504" are for actuating the rotary valve and plunger of cartridges 502, 502', 502 ". Automatic analyzer 500 is shown as having a means of relative motion 510 providing relative movement 512 between a reagent container or bucket 506 and cartridges 502, 502 'and 502 ". The 506 reagent container or cuvette is shown to contain a 508 biological sample. The 502, 502 ', 502 "cartridges can be used to add one or more liquids to the 508 biological sample. The automated analyzer 500 is shown to contain further a sensor system 514. The sensor system comprises one or more sensors for measuring a quantity or a physical, chemical or biochemical property of the biological sample 508. For example, the sensor system 514 may comprise a nuclear magnetic resonance (NMR) system , an optical reflectance or transmission measurement system, a pH meter, a camera system, a polymerase chain reaction (PCR) apparatus, an electrochemiluminescence (EQL) apparatus, a spectroscopic measurement system, a sensor electrochemical or optical and a chromatography system Relative motion means 510 may also be operated to move reagent container or cuvette 506 to sensor system 514.

The arrangement of cartridges 502, 502 ', 502 "and sensor system 514 is representative. In some embodiments, reagent container or cuvette 506 may remain in a fixed position and cartridges 502, 502', 502" are they can move. The drive systems 504, 504 ', 504 "and the sensor system 514 are shown as being connected to a computer interface 522 of a computer system 520. The computer system 520 functions as a controller for the automated analyzer 500. The Computer 520 is further shown as containing a processor 524 that can control the operation and function of automatic analyzer 500 using computer equipment interface 522. Processor 524 is shown as being further connected to user interface 526, computer storage 528 and computer memory 530. Computer memory 528 is shown as containing an analysis request 532. Analysis request 532 contains a request to analyze biological sample 508.

Computer storage 528 is shown to further contain sensor data 534 received from sensor system 514. Computer storage 528 is shown to further contain an analysis result 536 that was determined using sensor data 534. Computer memory 530 contains a control module 540. The control module 540 contains computer-executable code that enables the processor 524 to control the operation and function of the automatic analyzer 500. For example, the control module 540 may use the analysis request 532 to generate commands to be generated and sent to the drive systems 504, 504 ', 504 ", the sensor system 514 and the relative motion system 510. The control module 540 can also generate the analysis result 536 using the sensor data 534.

Various algorithms can be used to control the distribution of the liquid in different embodiments. For example, the actuator assembly can be controlled by the processor to perform a series of predetermined actions to distribute the liquid. In another example, a sensor or meter system could be integrated into the automatic analyzer to measure the distribution of the liquid. In this case, an algorithm that uses the actuator and sensor assembly to form a closed-loop feedback to accurately control or measure the distribution of the liquid.

Fig. 6 illustrates a bubble guiding structure 600 in accordance with one embodiment of the invention. The bubble guiding structure 600 may be located, for example, within a reservoir or secondary reservoir of a cartridge in accordance with one embodiment of the invention. The bubble guiding structure 600 comprises a bubble channel 602 surrounded by various liquid channels 604. The bubble channel 602 provides a path for a bubble 606. The liquid channels 604 have a space or width 608 that is narrow enough so that the bubble 606 is prevented from entering the liquid channel 604 by the surface tension of the liquid. Bubble channel 602 confines bubble 606 and allows the bubble to rise while allowing liquid 610 to surround the bubble.

Fig. 7 illustrates an automatic analyzer 700 in accordance with an embodiment that is similar to the embodiment shown in FIG. 5. The 700 Automatic Analyzer is similar to the 500 Automatic Analyzer shown in Figure 5. The automated analyzer 700 of Figure 7 additionally has a meniscus detector 702, 702 ', 702 ". Each meniscus detector 702, 702', 702" is positioned adjacent the outlet nozzle 126. The meniscus detectors 702, 702 ', 702 "are each connected to computer interface 522. This enables processor 524 to control actuator assemblies 504, 504', 504" to control the location of the meniscus. This, for example, may enable the processor to more accurately and / or reproducibly distribute liquid from cartridges 502, 502 ', 502 ".

Figure 8 shows 11 views 800, 802, 804, 806, 808, 810, 812, 814, 816, 818, 822 and illustrates the operation of a cartridge 100 in conjunction with a meniscus detector 702. In these examples, the meniscus 702 is an optical sensor. The use of the optical sensor 702 is exemplary. Other types of sensors can also be used.

In view 800, pump chamber conduit 120 has been rotated in position to align with reservoir conduit 124. In view 800, plunger 108 is shown as being fully depressed. Pump chamber 118 is therefore extremely small and is not visible in this view 800. Positioning of this plunger 108 in this position is not necessarily required as long as plunger 108 can still increase or withdraw a reasonable amount of liquid. 214 from reservoir 122. Then, in view 802, plunger 108 is withdrawn to increase the volume of pump chamber 118 and withdraw liquid 214 from reservoir 122 to pump chamber 118. Then, in view 804, conduit pump chamber 120 is rotated into position so that it lines up with outlet conduit 128.

In view 806, plunger 108 is depressed, decreasing the volume of pump chamber 118. This forces liquid 214 into outlet conduit 128 and outlet nozzle 126. Plunger 108 is controlled in accordance with the meniscus detector 702. When meniscus 822 reached a predetermined position, meniscus detector 702 was used to detect this and the pressure of plunger 108 was stopped. Then, in view 808, pumping chamber conduit 120 is rotated off. again in alignment with reservoir conduit 124. In view 810, plunger 108 is withdrawn, thereby increasing the volume of pump chamber 118 and drying liquid 214 in reservoir 122. Then, in view 812, the pump chamber conduit 120 is rotated in position so that it is aligned with the outlet conduit 128. The pump chamber 118 is filled with liquid and the meniscus a 22 is at the predetermined location. Then, in view 814, plunger 108 is depressed forcing liquid out of outlet nozzle 126. It can be seen in view 814 that liquid still exists within outlet conduit 128 and outlet nozzle 126. Then, at the view 816, plunger 108 retracts to draw liquid 214 that was in outlet conduit 128 and outlet nozzle 126 back to pump chamber 118, in view 818, pump chamber conduit 120 is rotated in position with reservoir conduit 124. Next, finally, in view 820-20, plunger 108 is depressed forcing liquid back into reservoir 122. A bubble 308 that was inside the pump chamber is forced outside the pump chamber and into reservoir 122.

Fig. 9 illustrates the correlation of target volume and measured volume for an embodiment of a rotary valve comprising a pump chamber volume of 10 µl. Fig. 9 shows a curve of the target volume (in pl) 900 versus the measured volume (in pl) 902. The measured points are connected by a linear fit indicated by the dashed line 904. Water was used as the test liquid for each data point . The measured volume has been determined using a graduated scale. Each data point indicates an average of three tests performed for the same target volume. In each trial or experiment, pumping was repeated 24 times. In other words, three trials or experiments were performed on each target volume. For each of these three experiments, the liquid was distributed 24 times and averaged. The data shown in fig. 9 illustrates both very high accuracy (small error bars, even for very small target volumes) and linearity (linear fit is very close to the ideal bisector line) over a large range of target volumes. which can be achieved using a rotary valve according to the invention.

Fig. 10 shows a curve indicating the accuracy and the coefficient of variation (CV) for the distribution of liquids by an embodiment of a rotary valve comprising a volume of the pumping chamber of 10 pl for liquids of different viscosities and voltages of surface. The X 1000 axis indicates the viscosity of 19 different A-S liquids in terms of mPas. The left Y-axis 1002 indicates the surface tension of each of these liquids in terms of mN / m. The viscosity vs. surface tension curve for each liquid is indicated by line 1004. The measured volume has been determined using a graduated scale. For each liquid, a test comprising 21 posterior distributions of a target volume of 1 µl was performed.

The right Y-axis 1006 indicates the accuracy of the distribution 1008 (left column, in%) and the coefficient of variation 1010 (right column, in%) for each liquid.

The data shown in fig. 10 illustrates that the distribution accuracy and reproducibility that can be achieved using a rotary valve according to the invention is very high and (almost) independent of the viscosity and / or surface tension of the liquid being distributes: if the accuracy and CV values of the different liquids A - S are compared taking into account their increasing viscosity (indicated on the X-axis), no effect of viscosity on both accuracy and CV can be identified. Furthermore, if the accuracy and CV values of the different liquids A - S are compared taking into account their respective surface tension (shown at 1004 and indicated on the left Y-axis), no effect of surface tension can be identified either. both about accuracy and CV.

Fig. 11 shows a cartridge 1100 according to one embodiment of the invention. The cartridge comprises a plunger 1108 that can slide within a piston 1114. The piston 1114 and a volume 1116 form a slide valve 1110. The volume 1116 can be formed in a housing 1117 or a portion of the cartridge 1100. The slide valve 1110 can perform a rectilinear movement. As the piston 1114 moves, there is a pump chamber passage 1120 that moves along with the piston 1114. There is a hole inside the piston 1114 in which the piston 1108 can move. This hole in the piston 1114 and Plunger 1108 form a pump volume 1118.

Piston 1114 can move pump chamber conduit 1120 to different locations. In this view, it is shown as being aligned with a reservoir conduit 1124. Reservoir conduit 1124 connects a reservoir 1122 filled with a liquid with pump chamber 1118. Reservoir 1122 is surrounded by a cartridge body 1112. In This position, the plunger 1134 can be moved so as to increase or decrease the volume of the pump chamber 1118. When the plunger 1108 is moved to increase the volume of the pump chamber 1118 when the piston 1114 is at this location, it is can draw liquid from reservoir 1122.

The piston 1114 can be moved so that the pump chamber conduit 1120 is aligned with an outlet conduit 1128. The outlet conduit 1128 provides access to an outlet nozzle 1126. When the pump chamber conduit 1120 is aligned with outlet conduit 1128, liquid can be expelled from pumping chamber 1118 through nozzle 1126 decreasing the volume of pumping chamber 1118.

In this embodiment, piston 1114 is shown as having a first mechanical piston stop 1130 and a second mechanical piston stop 1132. The piston in this example has a mechanical extension 1134 that can be operated to contact the first mechanical piston stop or the second mechanical piston stop. In this embodiment, the entire pumping arrangement can be realized only by actuating the plunger 1108. When the mechanical extension 1134 comes into contact with the first mechanical plunger stop 1130, the plunger 1108 can push the piston 1114 so that the conduit Pump chamber 1120 aligns with reservoir conduit 1124. When mechanical extension 1134 contacts second mechanical piston stop 1132, plunger 1108 can move piston 1114 so that pump chamber conduit 1120 is Aligns with outlet conduit 1128.

The first mechanical piston stop 1130, the second mechanical piston stop 1132 and the mechanical extension of the piston 1134 may not be present in all embodiments.

In an alternative embodiment, the cartridge may have a mechanical reservoir stop. The mechanical reservoir stop can come into contact with a contact surface. This provides a mechanical reservoir stop that roughly aligns pump chamber conduit 1120 with reservoir conduit 1124. In some embodiments, there may also be a mechanical outlet stop present and corresponding contact surface to align the chamber conduit. pumping with the outlet duct.

In an alternative embodiment, one end of volume 1116 may provide a mechanical stop to align pump chamber conduit 1120 with reservoir conduit. For example, in this example, volume 1116 is closed at one end with the exception of an air vent 1140. End surface 1142 may also be used in some embodiments as a mechanical stop for piston 1114.

In some embodiments, the plunger 1134 can be operated in the position of the piston 1114 without the use of the mechanical reservoir stopper or even a mechanical conduit stopper. For example, the surface between piston 1114 and volume 1116 can be constructed so that it is more difficult to move piston 1114 than it is piston 1108, for example, because static friction between piston 1114 and a housing 1117 of the volume 1116 is greater than the static friction between plunger 1108 and a corresponding portion of piston 1114 that forms the bore. In this case, the plunger 1108 can be moved without displacing the piston 1114 unless the plunger 1108 contacts one of the first mechanical piston stop 1130 or the second mechanical piston stop 1132.

Fig. 12 shows cartridge 1100 of FIG. 11 connected to an actuator assembly 1200. The actuator assembly 1200 comprises a linear actuator 1202 that moves along a linear track 1204 in the direction 1206. The linear actuator 1202 is connected by a coupling assembly 1208 to the plunger 1108 .

Fig. 13A shows another example of a cartridge 1300. The example in FIG. 13 is similar to that shown in FIGS. 11 and 12 with several additional characteristic features. In this embodiment, there is a secondary reservoir 1322. Secondary reservoir 1322 connects to a secondary reservoir conduit 1324 that can be aligned with pump chamber conduit 1120. There is an optional connection for a connecting conduit 1326 between the Reservoir 1122 and secondary reservoir 1322. In this example, there is also an optional membrane 1327 that covers the surface of connecting conduit 1326. Membrane 1327, for example, can prevent bubbles from secondary reservoir 1322 from entering reservoir 1122. This structure can be useful, for example, to pump liquid 1302 out of reservoir 1122 and return unused liquid 1302 to secondary reservoir 1322. Reservoir 1122 has optional vent 1328 and secondary reservoir 1322 has optional vent 1330. There is a wall side 1332 that divides the tank 1122 from the secondary tank 1322. In some embodiments, this dividing wall 1332 may not be present, in which case the primary tank forms a first part of the tank and the secondary tank 1322 forms a second part of the tank. Deposit. In this example, plunger 1108 and piston 1114 are actuated independently. Such a structure for plunger 1108 and piston 1114 can also be used as an alternative to the structure shown in FIG. eleven.

Fig. 13B shows an alternative example of a cartridge 1350 that is similar to cartridge 1300 shown in FIG.

13A. In the embodiment of fig. 13B, there is a separate tank 1122 'and a separate secondary tank 1322'. The connecting conduit 1326 of FIG. 13A is not present. The reservoir 1122 'may contain a first liquid 1302 and the secondary reservoir 1322' may contain a second liquid 1302 '. The first liquid 1302 and the second liquid 1322 'can be different liquids.

Fig. 14 shows cartridge 1300 in FIG. 13 connected to an actuator assembly 1400. In this embodiment, both plunger 1108 and piston 1114 are actuated independently. There is a linear actuator 1202 that moves along a linear track 1204 that connects to plunger 1108 by a coupling assembly 1208. There is a linear actuator 1402 that moves along linear track 1404 that connects to the piston 1114 by a coupling assembly 1408. Both linear actuators 1202 and 1402 are movable in direction 1206. The actual implementation of actuator assembly 1400 is intended to be representative and other actual constructions may also be used.

Figs. 15A and 15B show five different views 1500, 1502, 1504, 1506, 1508 of the slide valve 1110 with a plunger 1108 and piston 1114 of the embodiment shown in FIG. 11. Figs. 15A and 15B show an example of how piston 1114 and plunger 1108 can be used to pump liquid from reservoir chamber through outlet nozzle 1126. In view 1500, pump chamber passage 1120 is aligned with the reservoir conduit 1124. The volume of pumping chamber 1118 is at its minimum volume. The mechanical extension 1134 is in contact with the first mechanical piston stop 1130. Then, in view 1502, the piston 1108 is withdrawn in direction 1510. The piston is withdrawn until the mechanical extension 1134 contacts the second mechanical stop of plunger 1132. In this embodiment, piston 1114 requires more force to move than plunger 1108. In other words, plunger 1108 slides more easily than piston 1114. This could be accomplished by designing plunger 1108 so that has less friction than piston 1114. This enables piston 1114 and piston 1108 to be operated using a single actuator. The mechanical stops 1130 and 1132 are used to restrict the movement of the plunger 1108. The frictional force on the plunger causes the plunger 1108 to move first when a linear force is applied to the plunger 1108. When the plunger 1108 hits a stop mechanical 1130, 1132, then plunger 1108 and piston 1114 move together.

Pump chamber 1118 is filled with liquid from the liquid reservoir. Then, in view 1504, plunger 1108 is pulled out further. The mechanical extension 1134 is in contact with the second mechanical piston stop 1132 so that the piston 1108 exerts force on the piston 1114. The piston 1108 moves so far that the piston 1114 moves the pump chamber passage 1120 in alignment with outlet conduit 1128. Then, in view 1506, plunger 1108 moves in direction 1514. Liquid is forced out of pump chamber 1118 by plunger 1108 and through outlet conduit 1128. Liquid exits the outlet nozzle 1126 and forms droplets 1516 that exit the cartridge through outlet nozzle 1126.

Finally, in view 1508, plunger 1108 is further depressed 1516 so that mechanical extension 1134 exerts force on second mechanical plunger stop 1132 to force piston 1114 to align pump chamber conduit 1120 with reservoir conduit. 1124 again. In this embodiment, there is no mechanical stop to align the piston with reservoir passage 1124. This would most likely be done by controlling the plunger actuator 1108. View 1508 is substantially the same as view 1500. In this position, the pumping procedure can start over.

Figs. 16A and 16B illustrate an alternative embodiment to the slide valve 1110 of FIG. 11. In the embodiment shown in fig. 16A and 16B, the slide valve comprises a piston 1114 with a plunger 1108. The operation of this alternative embodiment is also illustrated in FIGS. 16A and 16B from views 1600, 1602, 1604, 1606 and 1608. In the embodiment shown in FIGS. 16A and 16B, the linear position of reservoir conduit 1124 and outlet conduit 1128 is reversed from that of FIG. 15A and 15B. Unlike the embodiment shown in fig. 15A and 15B, piston 1114 requires less force to move than piston 1108. In other words, piston 1114 slides more easily than piston 1108. This could be achieved by designing piston 1108 so that it has more friction than piston. 1114. As described below, mechanical stops 1130, 1132, 1609, and 1610 in combination with friction plunger 1108 allow pumping to be accomplished with a single actuator.

This embodiment has a mechanical outlet stop 1610 that aligns piston 1114 so that pump chamber conduit 1120 aligns with outlet conduit 1128. This embodiment also has a mechanical reservoir stop 1609 shown. as extending out of the slide valve 1110. The piston has a contact surface 1611. When the contact surface 1611 contacts the mechanical reservoir stop 1609, the reservoir conduit 1124 aligns with the chamber outlet. pumping 1120. There is also a Exit mechanical stop 1610 on slide valve 1110 operable to contact contact surface 1613. When exit mechanical stop 1610 contacts contact surface 1613, pump chamber conduit 1120 lines up with outlet conduit 1128.

In view 1600, pump chamber passage 1120 is aligned with reservoir passage 1124. Pump chamber 1118 is at its minimum and contact surface 1611 of piston 1114 is in contact with reservoir mechanical stop 1609. The slide valve 1110 is shown as having a first mechanical piston stop 1130 and a second mechanical piston stop 1132. When the mechanical extension 1134 is in contact with the first mechanical piston stop 1130, then the volume of the pumping chamber 1118 is at a minimum. When the mechanical extension 1134 is in contact with the second mechanical piston stop 1132, then the volume of the pump chamber 1118 is at a maximum.

The piston 1108 has its mechanical extension 1134 in contact with the first mechanical piston stop 1130. Then, in view 1602, the piston 1108 is withdrawn in direction 1612. The volume of the pump chamber 1118 is increased and the liquid is withdrawn. from the reservoir chamber until mechanical extension 1134 contacts second mechanical piston stop 1132. Mechanical reservoir stop 1609 prevents piston 1114 from moving during this.

Then, in view 1604, piston 1108 moves in direction 1614. The volume of pump chamber 1118 remains the same and contact surface 1613 of piston 1114 contacts mechanical outlet stop 1610. This aligns the passage. pump chamber 1120 with outlet conduit 1128.

Then, at step 1606, plunger 1108 is further depressed until mechanical extension 1134 contacts the first mechanical plunger stop. Piston 1114 is already in contact with outlet pump chamber conduit mechanical stop 1610. As plunger 1108 is depressed in direction 1616, piston 1114 cannot move further. Plunger 1108 then forces liquid out of pump chamber 1118 through outlet conduit 1128 and nozzle 1126. Liquid droplets 1516 are formed exiting the cartridge. Plunger 1108 can be depressed until mechanical extension 1134 contacts first mechanical piston stop 1130.

Then, at step 1608, plunger 1108 moves in direction 1618. Plunger moves in direction 1618 until contact surface 1611 of piston 1114 contacts mechanical reservoir stop 1609. Piston 1114 and plunger 1108 they are now in the same position they were in view 1600. The pump cycle is complete. This procedure can be repeated to pump more liquid 1516 out of the cartridge.

Fig. 17 shows two views 1700, 1702 of a combination slide valve 1110 and plunger 1108 which is an alternative to that shown in FIG. 11. In this embodiment there is no mechanical stop and piston 1114 and plunger 1108 can be operated independently. In view 1700, piston 1114 has moved so that pump chamber conduit 1120 is in alignment with reservoir conduit 1124. Liquid can be pumped into pump chamber 1118 by moving plunger 1108 outward. Liquid can also be moved back into reservoir conduit 1124. For example, used liquid can be moved back into reservoir chamber 1124 or plunger 1108 can be reciprocated to mix the liquid. View 1702 shows piston 1114 in a different position such that pump chamber conduit 1120 is in alignment with outlet conduit 1128. Piston 1108 can be moved in direction 1704 to pump liquid through outlet conduit 1128 and outlet nozzle 1126, thus forcing droplets 1516 of liquid out of the cartridge.

Figs. 18A and 18B illustrate one mode of operation of the slide valve 1110 of the embodiment shown in FIG. 13. The procedure illustrated in FIGS. 18A and 18B illustrate how the amount of liquid waste can be reduced during operation. This procedure is illustrated in eight different views, 1800, 1802, 1804, 1806, 1808, 1810, 1812, and 1814. Piston 1114 and plunger 1108 are operated independently. The procedure begins at view 1800. In view 1800, pump chamber conduit 1120 is aligned with reservoir conduit 1124. Plunger 1108 is in a position where pump chamber 1118 has a relatively small volume. In view 1802, plunger 1108 is withdrawn in direction 1816. This causes liquid to be withdrawn from the liquid reservoir into pump chamber 1118. Then, in view 1804, both plunger 1816 and piston 1818 are both withdrawn. simultaneously in sense 1820, 1818. Piston 1114 and plunger 1108 both move by the same amount. They both move until pump chamber conduit 1120 lines up with outlet conduit 1128.

Then, in view 1806, piston 1114 remains in the same position and plunger 1108 is depressed 1822. This forces the liquid out of the pump chamber 1118 and through the outlet conduit 1128. This forces the liquid in droplets 1516 out outlet nozzle 1126.

Then, in view 1808, to remove the remaining liquid within outlet conduit 1128, plunger 1108 is withdrawn in direction 1824 with piston 1114 remaining in the same position. Plunger 1108 has been pulled out 1824 enough so that most of the liquid has been removed from outlet conduit 1128. An amount of air may also be removed by also forming a bubble 1826. This results in a complete emptying of the outlet conduit. outlet 1128 of the remaining liquids and thus prevents the drying of liquid compounds within this conduit outlet 1128. Due to this complete emptying of outlet conduit 1128, no flushing or "priming" step is necessary before the next dispensing step, resulting in maximum efficiency of the use of the volume of liquid within the Deposit. Until now the amount of liquid used for cleaning purposes has been reduced; however, the presence of a bubble can cause inaccuracies in the liquid distribution.

Then, in view 1810, to eliminate this problem both piston 1114 and plunger 1108 are simultaneously withdrawn in direction 1830, 1832. Both piston 1114 and plunger 1108 move by the same amount. They move so that pump chamber conduit 1120 aligns with secondary reservoir conduit 1324.

Then, in view 1812, piston 1114 remains stationary and plunger 1108 is depressed in direction 1834. This forces bubble 1826 into the secondary reservoir. This has eliminated bubble 1826 from pump chamber 1118 and pump chamber conduit 1120. Bubble 1826 can no longer interfere with proper measurement of liquid in pump chamber 1118.

Finally, in view 1814, both piston 1114 and plunger 1108 are simultaneously depressed in direction 1836, 1838 by the same amount. The pump chamber outlet 1120 is again aligned with the reservoir conduit 1124 and the pump cycle is completed. The pump can be used again without the bubble 1826 interfering with the correct measurement or measurement of the liquid.

Fig. 19 illustrates an automated analyzer 1900 in accordance with one embodiment of the invention. This automated analyzer is shown as having three cartridges 1902, 1902 'and 1902 ". There is an actuator assembly 1904 connected to cartridge 1902. There is an actuator assembly 1904' assembled to cartridge 1902 '. There is an actuator assembly 1904" assembled to cartridge 1902 ". Actuator assemblies 1904, 1904 ', 1904" are for actuating the slide valve and plunger of cartridges 1902, 1902', 1902 ". Automatic analyzer 1900 is shown as having a means of relative motion 1910 providing relative motion 1912 between a 1906 reagent container or cuvette and cartridges 1902, 1902 'and 1902 ". The 1906 reagent container or cuvette is shown as containing a 1508 biological sample.

Cartridges 1902, 1902 ', 1902 "can be used to add one or more liquids to the 1908 biological sample. The 1900 automatic analyzer is shown to further contain a 1914 sensor system. The sensor system comprises one or more sensors to measure a amount or a physical, chemical, or biochemical property of the biological sample 1908. For example, the sensor system 1914 may comprise a nuclear magnetic resonance (NMR) system, an optical reflectance or transmission measurement system, a pH meter, a camera system, a polymerase chain reaction (PCR) apparatus, an electrochemiluminescence (EQL) apparatus, a spectroscopic measurement system, an electrochemical or optical sensor, and a chromatography system. The 1910 Relative Motion Medium is also used can be operated to move the 1906 reagent container or cuvette to the 1914 sensor system.

The arrangement of cartridges 1902, 1902 ', 1902 "and sensor system 1914 is representative. In some embodiments, the reagent container or cuvette 1906 can remain in a fixed position and cartridges 1902, 1902', 1902" they can move. The 1904, 1904 ', 1904 "drive systems and the 1914 sensor system are shown as being connected to a 1922 computer interface of a 1920 computer system. The 1920 computer system functions as a controller for the 1900 automatic analyzer. computer 1920 is further shown as containing a 1924 processor that can control the operation and function of the 1900 automatic analyzer using the 1922 computer equipment interface. The 1924 processor is shown as being further connected to a 1926 user interface, computer storage 1928 and 1930 computer memory. The 1928 computer memory is shown as containing a 1932 test request. The 1932 test request contains an application to test the 1908 biological sample.

The 1928 computer storage is shown as further containing 1934 sensor data received from the 1914 sensor system. The 1928 computer storage is shown as further containing a 1936 analysis result that was determined using the 1934 sensor data. The 1930 computer memory contains a control module 1940. The control module 1940 contains computer-executable code that enables the processor 1924 to control the operation and function of the automatic analyzer 1900. For example, the control module 1940 can use the request for analysis 1932 to generate commands to be generated and sent to the drive systems 1904, 1904 ', 1904 ", the sensor system 1914 and the relative motion system 1910. The control module 1940 can also generate the analysis result 1936 using the sensor data 1934.

Various algorithms can be used to control the distribution of the liquid in different embodiments. For example, the actuator assembly can be controlled by the processor to perform a series of predetermined actions to distribute the liquid. In another example, a sensor or meter system could be integrated into the automatic analyzer to measure the distribution of the liquid. In this case, an algorithm that uses the actuator and sensor assembly to form a closed-loop feedback to accurately control or measure the distribution of the liquid.

Fig. 20 illustrates an automatic analyzer 2000 in accordance with an embodiment of the invention that is similar to the embodiment shown in FIG. 19. The Automatic Analyzer 2000 is similar to the Automatic Analyzer 1900 shown in Fig. 19. The automated analyzer 2000 of FIG. 20 additionally has a meniscus detector 2002, 2002 ', 2002 ". Each meniscus detector 2002, 2002', 2002" is positioned adjacent to outlet nozzle 1126. Meniscus detectors 2002, 2002 ', 2002 "are connected each one to computer interface 1922. This enables processor 1924 to control actuator assemblies 1904, 1904 ', 1904 "to control the location of the meniscus. This, for example, may enable the processor to more precisely and / or reproducibly distribute liquid from cartridges 1902, 1902 ', 1902 ".

Fig. 21 shows another example of a cartridge 2100. The cartridge 2100 shown in FIG. 21 is similar to that shown in FIG. 11. Cartridge 2100 shown in FIG. 21 comprises two pieces. There is a buildable tank 2102 and a pump unit 2104. The pump unit 2104 has a first connection 2106 and the buildable tank 2102 has a second connection 2108. The first connection 2106 can be operated to connect to the second connection 2108. This assembles the buildable reservoir 2102 to the pump unit 2104. The buildable reservoir 2102 in this example is shown as having a vent 1328. Near the second assembly 2108, the reservoir 1122 is sealed with a seal 2110. Near the first connection 2106 There is a knife edge 2112 that can be operated to open the seal 2110 when the first connection 2106 is connected to the second connection 2108.

The embodiment shown in fig. 21 enables more flexibility and economy in preparing multiple cartridges. For example, the volume of the buildable reservoir could be varied, as well as the type of liquid that fills the reservoir 1122. The pump unit 2104 can also be varied. For example, the diameter of plunger 2108 could be varied, as well as its stroke. This may allow a more accurate pump unit or a high volume pump to be selected.

Figs. 22 through 25 show various embodiments of slide valve 1110. All of the embodiments shown in FIGS. 22-25 show a plunger 1108 with a mechanical extension 1134 on the plunger. The piston 1114 in each of these embodiments has a first mechanical piston stop 1130 and a second mechanical piston stop 1132 as described in FIG. eleven.

The embodiment of the slide valve 1110 shown in FIG. 22 has no air vent 1140. There is also no mechanical tank stop or mechanical outlet stop. Precise alignment of pump chamber conduit 1120 with reservoir conduit 1124 or outlet conduit 1128 can be accomplished or provided by an actuator.

In fig. 23, the slide valve 1110 is shown as comprising an air vent 1140 as shown in FIG. 11. Slide valve 1110 is shown as comprising a reservoir mechanical stop 1609 for contacting a surface 1611 of piston 1114. Reservoir mechanical stop 1609 aligns pump chamber conduit 1120 with reservoir conduit 1124. However, there is no mechanical stop that aligns outlet conduit 1128 with pump chamber conduit 1120. Precise alignment of pump chamber conduit 1122 and outlet conduit 1128 can be accomplished by a linear actuator.

In fig. 24 an air vent is not shown. In the embodiment shown in fig. 24, the slide valve 1110 comprises an outlet mechanical stop 1610 for contacting a surface 1613 of the piston 1114. The outlet mechanical stop 1610 can be operated to align the outlet conduit 1128 with the pump chamber conduit 1120 However, there is no mechanical stop to align the pump chamber conduit 1120 with the reservoir conduit 1124. Precise alignment of the reservoir conduit can be provided by a linear actuator.

In fig. 25 an air vent 1140 is shown. The embodiment shown in FIG. 25 comprises a reservoir mechanical stop 1609 for contacting a surface 1611 of piston 1114. Reservoir mechanical stop 1609 aligns pump chamber conduit 1120 with reservoir conduit 1124. The embodiment shown in FIG. 25 also shows a mechanical outlet stopper 1610 on the slide valve 1110. The mechanical outlet stopper 1610 can be operated to contact the cutting surface 1613 of piston 1114. The mechanical outlet stopper 1610 can be operated to aligning pump chamber conduit 1120 with outlet conduit 1128.

The examples shown in Figs. 22-25 are exemplary and not all possible combinations of how the slide valve 1110 could be constructed. For example, the relative position of the reservoir conduit 1124 and the outlet conduit 1128 could be linearly juxtaposed.

Figs. 26 and 27 illustrate how friction between plunger 1108 and piston 1114 can be increased. In FIG. 26, the slide valve 1110 is shown as having a vent 1110 as shown in FIG. 11. Slide valve 1110 further comprises a reservoir mechanical stop 1610 and outlet mechanical stop 1609 for contacting piston 1114. As previously described, these mechanical stops 1609, 1610 serve to align the pump chamber conduit 1120 with the tank line 1124 and the outlet line 1128. The Plunger 1108 is shown as having mechanical extensions 1134. However, in the embodiment shown in FIG. 26, there is no first mechanical piston stop 1130 and no second mechanical piston stop 1132 as previously shown. The mechanical extensions 1134 come into contact with a surface 2600 within the piston 1114. The mechanical extension 1134 and the contact surface 2600 increase the friction between the piston 1108 and the piston 1114. This enables the piston 1114 to be actuated by the movement of the piston. plunger 1108. Since there is no mechanical plunger stop in this embodiment, the movement of plunger 1108 will be controlled by a linear actuator.

Fig. 18 shows an embodiment of a slide valve 1110 similar to that shown in FIG. 26. The embodiment shown in fig. 27 is similar to that shown in FIG. 26 except with the addition of a first mechanical piston stop 1130 and a second mechanical piston stop 1132 to limit the travel of the piston 1108 relative to the piston 1114. The mechanical extensions 1134 still contact a surface 2600, which increases the friction between plunger 1108 and piston 1114. This enables piston 1114 to be driven by plunger 1108.

Reference number list

100 cartridge

102 actuator assembly

104 linear actuator

105 direction of linear movement

106 rotary actuator

107 direction of rotation movement

108 plunger

110 rotary valve

112 cartridge body

114 cylindrical part

116 cylindrical space

118 pumping chamber

120 pump chamber duct

122 tank

124 reservoir pipe

126 outlet nozzle

128 outlet duct

130 actuator assembly

200 first sight

202 second sight

204 third view

206 fourth view

208 pulled plunger

210 rotary valve turned

212 plunger pressed

liquid

fifth view

sixth view

seventh view

plunger removed

bubble

rotary valve turned

depressed plunger

first glance

second sight

third sight

fourth sight

fifth view

sixth view

seventh view

cartridge

secondary deposit

connection pipe secondary tank pipe automatic analyzer

cartridge

'cartridge

"cartridge

actuator assembly

'actuator assembly

"receptacle or cuvette actuator assembly with biological sample reagent

means of relative motion relative motion

sensor system

computer

computer interface 524 processor

526 user interface

528 computer storage

530 computer memory

532 request for analysis

534 sensor data

536 scan results

540 control module

600 bubble guiding structure 602 bubble channel

604 liquid channel

606 bubble

608 space

610 liquid

700 automatic analyzer

702 meniscus detector

800 rotary valve turned

802 pulled plunger

804 rotary valve turned

806 plunger pressed

808 rotary valve turned

810 plunger removed

812 rotary valve turned

814 plunger pressed

816 plunger removed

818 rotary valve turned

820 plunger pressed

900 target volume

902 measured volume

904 linear fit

1000 viscosity

1002 surface tension

1004 viscosity vs. surface tension 1006 percent

1008 accuracy

1010 coefficient of variation (CV) 1100 cartridge

1108 plunger

1110 slide valve

1112 cartridge body

1114 piston

1116 volume

1117 accommodation

1118 pumping chamber

1120 pumping chamber conduit 1122 reservoir

1122 'tank

1124 tank pipe

1126 outlet nozzle

1128 outlet duct

1130 first mechanical piston stop 1132 second mechanical piston stop 1134 mechanical piston extension 1140 air vent

1142 inner surface

1200 actuator assembly

1202 linear actuator

1204 linear track

1206 direction of actuation

1208 actuator assembly

1300 cartridge

1302 liquid

1302 'liquid

1322 secondary tank

1322 'secondary tank

1324 secondary tank pipe 1326 connecting duct

1327 membrane

1328 ventilation

1330 ventilation

1332 partition wall

1400 actuator assembly

1402 linear actuator

1404 linear track

1408 actuator assembly

1500 view of slide valve and plunger 1502 view of slide valve and plunger 1504 view of slide valve and plunger 1506 view of slide valve and plunger 1508 view of slide valve and plunger 1510 drawn plunger

1512 plunger removed

1514 plunger pressed

1516 droplet

1600 view of slide valve and plunger 1602 view of slide valve and plunger 1604 view of slide valve and plunger 1606 view of slide valve and plunger 1608 view of slide valve and plunger 1609 mechanical reservoir stop

1610 mechanical exit stop

1611 contact surface

1612 plunger removed

1613 contact surface

1614 plunger pressed

1616 plunger pressed

1618 plunger removed

1700 view of slide valve and plunger 1702 view of slide valve and plunger 1704 plunger pressed

1800 view of slide valve and plunger 1802 view of slide valve and plunger 1804 view of slide valve and plunger 1806 view of slide valve and plunger 1808 view of slide valve and plunger 1810 view of slide valve and plunger 1812 view of slide valve and plunger 1814 view of slide valve and plunger 1816 plunger removed

1818 plunger removed

1820 piston removed

1822 plunger pressed

1824 plunger removed

1830 piston removed

1832 plunger removed

1834 plunger pressed

1836 pressed piston

1838 pressed plunger

1900 automatic analyzer

1902 cartridge

1902 'cartridge

1902 "cartridge

1904 actuator assembly

1904 'actuator assembly

1904 "actuator assembly

1906 receptacle or cuvette with reagent 1908 biological sample

1910 means of relative motion 1912 relative motion

1914 sensor system

1920 computer

1922 computer equipment interface 1924 processor

1926 user interface

1928 computer storage 1930 computer memory 1932 analysis request

1934 sensor data

1936 analysis result 1940 control module

2000 automatic analyzer 2002 meniscus detector 2002 'meniscus detector

Claims (12)

1. A cartridge (1100, 1300, 1350, 1902 ', 1902 ") for dispensing liquid (1302, 1302', 1516), comprising: - a tank (1122) filled with liquid; - a reservoir conduit (1124) for connecting the reservoir with a valve; - an outlet conduit (1128) to distribute the liquid; Y - the valve (1100), in which the valve is a sliding valve (1110), in which the valve comprises a pumping chamber (1118) for pumping the liquid, in which the valve comprises a pumping chamber conduit (1120), in which the slide valve is configured to translate the pumping chamber conduit (1120), wherein the valve is configured to locate the pumping chamber conduit to connect with the reservoir conduit, wherein the valve is further configured to locate the chamber conduit pumping chamber to connect with the outlet conduit, in which the pump chamber conduit is permanently connected to the pumping chamber, in which the slide valve comprises a piston (1114) and a housing (1117) having a volume (1116) to receive the piston, in which the piston can be operated for translational movement within the volume, in which the piston comprises the pumping chamber conduit, in which the pumping chamber is a cavity within of the piston, wherein the piston is configured to translate the pumping chamber conduit to connect with the reservoir conduit and disconnect from the outlet conduit, wherein the piston is further configured to transport slating the pumping chamber conduit to connect with the outlet conduit and disconnect from the reservoir conduit; Y - a piston (1108) arranged in a part of the piston that forms the cavity, the piston being configured to change a volume of the pumping chamber, in which the pumping chamber is formed by the cavity and the plunger, in which the static friction between the piston and the volume housing (1117) to receive the piston is greater than the static friction between the plunger and the part of the piston that forms the cavity. The cartridge of claim 1, wherein the cartridge further comprises a return conduit (1324) connected to the reservoir, wherein the pump chamber conduit is operable to receive liquid via the reservoir conduit, wherein the return conduit is operable to return liquid to a second part (1322) of the reservoir, wherein the slide valve is further operable to translate the pump chamber conduit to connect to the return conduit. The cartridge of claim 1 or 2, wherein the cartridge further comprises: - a secondary tank (1322 '); Y - a secondary reservoir conduit (1324), in which the slide valve can be further operated to translate the pumping chamber conduit to connect to the secondary reservoir conduit. The cartridge of claim 3, wherein the cartridge further comprises a connecting conduit, wherein the connecting conduit is operable to transport liquid between the secondary reservoir and the reservoir, and wherein the cartridge comprises a membrane that blocks the connecting conduit, and in which the membrane is permeable to liquid. The cartridge of any one of claims 1 to 4, wherein the cartridge further comprises a coupling assembly for assembling the slide valve and plunger to an actuator assembly. The cartridge of any one of the preceding claims, wherein the slide valve comprises a mechanical reservoir conduit stop (1609) for aligning the pumping chamber conduit with the reservoir conduit and / or a mechanical conduit stop outlet (1610) to align the pump chamber conduit with the outlet conduit and / or wherein the piston comprises two mechanical plunger stops (1130, 1132) to limit movement of the plunger relative to the piston, wherein the plunger is operable to actuate the piston. 7. An automatic analyzer (1900, 2000) to analyze a biological sample (1908), comprising: a cartridge according to any one of the preceding claims; - an actuator assembly (1200, 1400, 1904, 1904 ', 1904 ") connected to the cartridge and configured to actuate the plunger and the valve; and - a controller (1920) to control the operation of the actuator assembly. The automated analyzer of claim 7, wherein the cartridge comprises an outlet nozzle (1126), wherein the automated analyzer further comprises a meniscus detector (2002, 2002 ', 2002 ") to detect a meniscus of the liquid, in which the controller is configured to: - control the actuator assembly to force liquid through the outlet nozzle; - detect the meniscus using the meniscus detector; Y - controlling the actuator to stop liquid from being forced through the outlet when the meniscus is at a predetermined location. The automated analyzer of claim 7 or 8, wherein the controller is configured to: - controlling (1516, 1618, 1836, 1838) the actuator assembly to translate the pumping chamber conduit to connect with the reservoir conduit by translating the slide valve; - controlling (1510, 1612, 1816) the actuator assembly to fill the pump chamber by increasing the volume of the pump chamber with the plunger; - controlling (1512, 1614, 1818, 1820) the actuator assembly to translate the pumping chamber conduit to connect with the outlet conduit by translating the slide valve; Y - controlling (1514, 1616, 1704, 1822) the actuator assembly to pump the liquid through the outlet conduit by decreasing the volume of the pumping chamber with the plunger. A method of operating a cartridge according to any one of claims 1 to 6, wherein the method comprises the steps of: - translating (1516, 1618, 1836, 1838) the piston to translate the pumping chamber conduit to connect with the reservoir conduit and disconnect from the outlet conduit; - increasing (1510, 1612, 1816) the volume of the pumping chamber with the plunger to fill the pumping chamber; - translating (1512, 1614, 1818, 1820) the piston to translate the pumping chamber conduit to disconnect from the reservoir conduit and connect with the outlet conduit; Y - decrease (1514, 1616, 1704, 1822) the volume of the pumping chamber with the plunger to pump the liquid through the outlet conduit. The method of claim 10, wherein the method further comprises recovering the liquid from the outlet conduit by increasing (1824) the volume of the pump chamber with the plunger. The method of claim 10 or 11, wherein the method further comprises the steps of: - translating (1830, 8132) the pumping chamber conduit to connect with the reservoir conduit by translating the slide valve; Y - returning (1834) the liquid to the reservoir decreasing the volume of the pumping chamber with the plunger.